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Thyroid and Adrenal Glands

2. Adrenal Glands

2.3. Regulation of Adrenal Cortex Hormones

  • The adrenal cortex maintains homeostasis through the secretion of mineralocorticoids, glucocorticoids, and androgens.
  • Each hormone class is regulated by distinct mechanisms that respond to systemic needs such as stress, electrolyte balance, and metabolic demand.
1. Regulation of Mineralocorticoids (Aldosterone) – Zona Glomerulosa

Main Hormone: Aldosterone
Primary Role: Controls sodium and potassium balance and maintains extracellular fluid volume and blood pressure.

Regulatory Mechanisms

1.     Renin–Angiotensin–Aldosterone System (RAAS):

  • The most important regulatory pathway.
  • Low blood pressure, low blood volume, or low sodium concentration stimulates the kidney’s juxtaglomerular cells to release renin.
  • Renin converts angiotensinogen (from the liver) → angiotensin I, which is then converted by angiotensin-converting enzyme (ACE) → angiotensin II.
  • Angiotensin II directly stimulates the zona glomerulosa to secrete aldosterone.
  • Aldosterone increases Na⁺ reabsorption and K⁺ excretion in the kidneys, restoring blood pressure and fluid balance.

2.     Plasma Potassium Concentration:

  • Elevated K⁺ levels directly stimulate aldosterone secretion.
  • Decreased K⁺ inhibits it.

3.     ACTH (Adrenocorticotropic Hormone):

  • Plays a minor role by transiently enhancing aldosterone secretion.
2. Regulation of Glucocorticoids (Cortisol) – Zona Fasciculata

Main Hormone: Cortisol
Primary Role: Regulates glucose metabolism, immune response, and adaptation to stress.

Regulatory Mechanisms

1.     Hypothalamic–Pituitary–Adrenal (HPA) Axis:

  • Stress or circadian rhythms stimulate the hypothalamus to release corticotropin-releasing hormone (CRH).
  • CRH acts on the anterior pituitary, triggering release of ACTH.
  • ACTH stimulates the zona fasciculata to synthesize and secrete cortisol.

2.     Negative Feedback Control:

  • Elevated cortisol levels inhibit CRH release from the hypothalamus and ACTH release from the pituitary.
  • This feedback loop maintains cortisol within normal physiological limits.

3.     Circadian Rhythm:

  • Cortisol secretion follows a diurnal pattern, peaking in the early morning and reaching its lowest level at midnight.
  • This rhythm aligns metabolic activity with daily energy demands.
3. Regulation of Adrenal Androgens – Zona Reticularis

Main Hormones: Dehydroepiandrosterone (DHEA) and Androstenedione
Primary Role: Act as precursors for sex steroids and influence secondary sexual characteristics.

Regulatory Mechanisms

1.     ACTH-Dependent Secretion:

  • The zona reticularis responds to ACTH, similar to the zona fasciculata.
  • Increased ACTH enhances androgen synthesis, while low ACTH reduces it.

2.     Lack of Strong Feedback Control:

  • Unlike cortisol, adrenal androgens do not exert significant negative feedback on CRH or ACTH.
  • Their levels depend largely on the activity of the HPA axis.
Key Takeaway

  • Cortisol regulation is mainly under the HPA axis with strong feedback control.

  • Aldosterone secretion is governed by the RAAS and plasma K⁺ concentration.

  • Adrenal androgens follow ACTH influence but lack tight feedback regulation.

  • Disruptions in these regulatory pathways lead to clinically significant adrenal disorders with characteristic hormonal and systemic effects.